GLP-1R agonist therapy for diabetes: benefits and potential risks

Curr Opin Endocrinol Diabetes Obes. 2013 Apr;20(2):87-97. doi: 10.1097/MED.0b013e32835edb32.


Purpose of review: Glucagon-like peptide 1 receptor (GLP-1R) agonists provide good glycemic control combined with low hypoglycemia risk and weight loss. Here, we summarize the recently published data for this therapy class, focusing on sustainability of action, use in combination with basal insulin, and the efficacy of longer acting agents currently in development. The safety profile of GLP-1R agonists is also examined.

Recent findings: GLP-1R agonists provide sustained efficacy and their combination with basal insulin is well tolerated, providing additional glycemic control and weight benefits compared with basal insulin alone. Data suggest that the convenience of longer acting agents may be at the expense of efficacy. Despite the initial concerns, most evidence indicates that GLP-1R agonists do not increase the risk of pancreatitis or thyroid cancer. However, the extremely low incidence of these events means further investigations are required before a causal link can be eliminated. Large-scale clinical trials investigating the long-term cardiovascular safety of this therapy class are ongoing and may also provide important insights into pancreatic and thyroid safety.

Summary: GLP-1R agonists offer sustained glycemic efficacy, weight loss benefits, and a low risk of hypoglycemia. The results of ongoing trials should help to clarify the safety of this therapy class.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't
  • Review

MeSH terms

  • Blood Glucose / drug effects
  • Blood Glucose / metabolism
  • Diabetes Mellitus, Type 1 / blood
  • Diabetes Mellitus, Type 1 / complications
  • Diabetes Mellitus, Type 1 / drug therapy*
  • Diabetes Mellitus, Type 2 / blood
  • Diabetes Mellitus, Type 2 / complications
  • Diabetes Mellitus, Type 2 / drug therapy*
  • Diabetic Angiopathies / chemically induced*
  • Exenatide
  • Female
  • Glucagon-Like Peptide 1 / agonists*
  • Glucagon-Like Peptide 1 / analogs & derivatives
  • Glucagon-Like Peptide 1 / therapeutic use
  • Glucagon-Like Peptides / analogs & derivatives
  • Humans
  • Hypoglycemia / chemically induced
  • Hypoglycemic Agents / adverse effects
  • Hypoglycemic Agents / therapeutic use*
  • Immunoglobulin Fc Fragments / therapeutic use
  • Insulin / therapeutic use
  • Liraglutide
  • Male
  • Pancreatitis / chemically induced*
  • Peptides / therapeutic use
  • Randomized Controlled Trials as Topic
  • Recombinant Fusion Proteins / therapeutic use
  • Thyroid Neoplasms / chemically induced*
  • Treatment Outcome
  • Venoms / therapeutic use


  • Blood Glucose
  • Hypoglycemic Agents
  • Immunoglobulin Fc Fragments
  • Insulin
  • Peptides
  • Recombinant Fusion Proteins
  • Venoms
  • rGLP-1 protein
  • Glucagon-Like Peptides
  • lixisenatide
  • Liraglutide
  • Glucagon-Like Peptide 1
  • Exenatide
  • dulaglutide